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Synthetic methodology

Arene additions

Nature Chemistry volume 15, pages 745–746 (2023)Cite this article

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Dipolar cycloadditions are excellent processes for generating heterocyclic systems from simple starting materials, but arenes as dipolarophiles have not been extensively explored. Now, the intramolecular dipolar cycloaddition of aromatic rings has been achieved using in situ generated diazoalkenes to produce bicyclic or tricyclic heterocycles.

Cycloadditions are some of the best strategies to generate heterocyclic structures from relatively simple starting materials, with dipolar cycloadditions being a reputable method to generate five-membered rings, including the copper-catalysed azide–alkyne cycloaddition reaction that is often synonymous with click chemistry1,2. Throughout history, a variety of dipoles have been used in dipolar cycloadditions, including azides, diazoalkanes, nitrile oxides, and nitrile imines. These dipoles have been shown to react with dipolarophiles such as alkynes, alkenes, and arynes, but arenes have remained elusive. Presumably, the stabilization that is typical of aromatic rings renders these systems unreactive in dipolar cycloaddition reactions. Now, writing in Nature Chemistry, Valery Fokin and co-workers present a strategy to overcome this limitation, where arenes react with in situ generated diazoalkenes in an intramolecular dipolar cycloaddition3. The instability of diazoalkenes is exploited to compensate for the stability of arenes — to traverse an activation barrier that is otherwise too high.

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Fig. 1: Mechanistic analysis for the conversion of sulfonyl azides and lithium acetylides to Sultams, SulfoIns and NH-triazoles.

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  1. Twitter: @MitchCroatt

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  1. Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, NC, USA

    Abraham Ustoyev & Mitchell P. Croatt

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  1. Abraham Ustoyev
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Correspondence to Mitchell P. Croatt.

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Ustoyev, A., Croatt, M.P. Arene additions. Nat. Chem. 15, 745–746 (2023). https://doi.org/10.1038/s41557-023-01190-5

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